title: Poly(ethylene glycol) versus dendrimer prodrug conjugates: influence of prodrug architecture in cellular uptake and transferrin mediated targeting.
abstract: Many polymer based drug delivery nanosystems are currently being explored for delivering cytotoxic agents to the tumors. However, very few strategies delineate the comparative carrier ability of nanosystems, in similar experimental settings. As a result, it remains unclear how to optimally design polymer based multicomponent prodrug systems for delivery applications. The present study is aimed to design polymeric prodrug conjugate carriers for the comparative cellular delivery ability of anticancer drug doxorubicin hydrochloride (DOX) using linear poly(ethylene glycol) (PEG), hyperbranched poly(amido amine) (PAMAM) G4 dendrimer, and PAMAM G4 dendrimer-PEG conjugate using MCF-7 cells. Furthermore, the cellular targetability and in vitro anticancer activity of DOX conjugates is evaluated using transferrin (Tf) as a targeting ligand. Interestingly, conjugation of DOX to PAMAM G4-OH dendrimer significantly influences the cytotoxicity of DOX leading to -4 fold decrease in the IC50 dose when compared to pegylated DOX. This study establishes the rational and comparative structural activity relationship of polymeric prodrug carriers for delivery of anticancer drugs. The schematic representation of design of prodrug conjugates with varied polymeric architecures is as shown below (Fig. 1).
authors.affiliation: NCE-Polymer Chemistry Group, Piramal Healthcare Ltd., Goregaon, Mumbai 400063, India.
authors.forename: Naval
authors.initials: N
authors.lastname: Aher
authors.forename: Shashwat
authors.initials: S
authors.lastname: Banerjee
authors.forename: Sujit
authors.initials: S
authors.lastname: Bhansali
authors.forename: Rajesh
authors.initials: R
authors.lastname: Yadav
authors.forename: Mahesh
authors.initials: M
authors.lastname: Shidore
authors.forename: Satish
authors.initials: S
authors.lastname: Mhaske
authors.forename: Rohit
authors.initials: R
authors.lastname: Chaudhari
authors.forename: Sneha
authors.initials: S
authors.lastname: Asai
authors.forename: Archana
authors.initials: A
authors.lastname: Jalota-Badhwar
authors.forename: Jayant
authors.initials: J
authors.lastname: Khandare
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002477:Cells / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D011108:Polymers; D011355:Prodrugs; D014168:Transferrin; D011092:Polyethylene Glycols; D004317:Doxorubicin